Research that uses powerful gene-editing techniques on human embryos needs to be restricted,
scientists agree — but they are split over why.

Some say that if safety fears can be allayed, such applications could have a bright
future, and could help to eradicate devastating diseases. Others say that modifying
the DNA of embryos, which means that the changes could be passed on to future generations,
is an ethical line that should not be crossed.

The concerns are laid out in an article1 published in Nature on 12 March and in one expected to appear in Science, amid suspicions that scientists have already edited the genes of human embryos.

Gene-editing techniques use enzymes called nucleases to snip DNA at specific points
and then delete or rewrite the genetic information at those locations. Most recently,
excitement has focused on a technique called CRISPR/Cas9, which is particularly easy
to use. Current applications of the technology are in non-reproductive, or somatic,
cells: for example, Sangamo BioSciences of Richmond, California, has used zinc-finger
nucleases, an older gene-editing technology, to remove a gene from white-blood cells
that encodes the receptor to which HIV binds to enter the cells.

But concerns focus on the use of gene editing to modify the genomes of eggs and fertilized
eggs — a process known as germline modification.

Edward Lanphier, president of Sangamo and chairman of the Alliance for Regenerative
Medicine in Washington DC, together with colleagues from both organizations, wrote
the Comment article1 in Nature calling on scientists not to modify human embryos, even in research. The authors
warn that such work could be exploited for “non-therapeutic modifications” — to change
a child’s eye colour, for example — and that a public outcry about such an “ethical
breach” could hinder the use of gene editing in somatic cells.

They also have more basic objections. “We are humans, not transgenic rats,” says Lanphier.
“We believe there is a fundamental ethical issue in crossing the boundary to modifying
the human germ line.”

George Church, a geneticist at Harvard Medical School in Boston, Massachusetts, agrees
that there should be a moratorium on embryo editing, but only “until safety issues
are cleared up and there is general consensus that it is OK”. Church, along with a
group of scientists who met in Napa, California, in January to discuss the ethics
and potential of the procedure, authored the piece for publication in Science detailing their concerns.

One concern is that nucleases could make mutations at locations other than those targeted,
potentially causing disease. Church says that gene editing in animals is likely to
reveal how to understand and avoid this complication. In one application, his group
is editing genes related to the immune system in pig embryos to ‘humanize’ them, potentially
allowing the pig’s organs to be transplanted into people.

Other indications of safety will come from trials on somatic cells. Sangamo has already
demonstrated the safety of its modified white-blood cells in a clinical trial of people
with HIV2.

Church sees no fundamental problem with editing the germ line — he notes that even
the somatic-cell therapies are still a form of artificial modification. He compares
gene editing in embryos to in vitro fertilization, which people objected to until it was shown to be safe.

“In the distant future, I could imagine that altered germ lines would protect humans
against cancer, diabetes and other age-related problems,” says Nobel-prizewinning
geneticist Craig Mello of the University of Massachusetts in Worcester. In the nearer
term, “there could be good reason to experiment with discarded embryos or embryonic
stem cells for research purposes”, he says.

But Lanphier says that for most cases in which parents carry disease-causing genes,
not all of a couple’s embryos will carry the faulty gene. Existing technology can
be used to genetically screen and select healthy embryos before transplantation into
the uterus, negating the need for permanent germline repair. “There are almost always
alternatives,” he says.

Church, however, says that for the growing number of known cases in which several
genes are involved in a disease, most embryos need to be discarded. Editing would
greatly increase the odds of getting a healthy embryo.

Dana Carroll, a geneticist at the University of Utah in Salt Lake City who was at
the Napa meeting, says that a national agency such as the US National Academy of Sciences
should convene a conference that includes medical professionals and the interested
public to weigh up the positive and negative aspects of germline editing. They had
better hurry: several researchers who do not want to be named told Nature’s news team that papers describing such work are currently being considered for publication
in journals.

Carroll also cites the importance of educating the next generation of physicians about
gene editing. “They should be learning now what the technology is able to do and what
the social, as well as clinical, concerns are.”